PROJECT SUMMARY GENOME AND SINGLE CELL TECHNOLOGIES The key function of The Jackson Laboratory Cancer Center (JAXCC) Genome and Single Cell Technologies Shared Resource (GSCT) is the provision of genomic technologies to sequence the genomic structures (DNA, RNA, epigenome) and to precisely define the molecular features of individual cells. GSCT is composed of two integrated components that are each part of JAX's institutionally managed Scientific Services program: Genome Technologies, led by Dr. Chia-Lin Wei, and Single Cell Biology, led by Dr. Paul Robson. GSCT provides a continuum of methods to address complex questions in cancer genomics and genomic biology. Key capabilities include a suite of molecular biology protocols; diverse platforms for DNA sequencing; and streamlined data management and analysis systems developed in conjunction with the Computational Sciences Shared Resource. Sequencing includes first generation Sanger sequencing, second-generation high-throughput short- read, and third-generation single molecule long-read sequencing services. The expansion of the Shared Resource to include Single Cell Biology broadens the repertoire of platforms to include droplet-based single cell transcriptomic and epigenomic sequencing. GSCT also continually develops new methods, and identifies and brings in the best externally developed methods, often in close collaboration with JAXCC members. GSCT keeps all JAXCC members abreast of the latest available technologies through seminars, workshops, one-on-one meetings, and directly through hands-on training of JAXCC member trainees. GSCT thus provides comprehensive, high quality and effective solutions for JAXCC members to profile cancers using whole genome, epigenome and transcriptome sequencing approaches and spatially resolved cellular phenotyping. In the next funding cycle, our goal is to continue to provide genomic and single cell technology support and ensure JAXCC members have access to the platforms they need to investigate the genomic instability and genetic complexity of cancer and the molecular interactions between a tumor and host that contribute to cancer biology. Our Specific Aims are to: 1) Incorporate new efficiencies to improve GSCT operations and enhance value to JAXCC members; 2) Provide JAXCC members with new genomic technologies for multi-dimensional genome analyses; and 3) Provide the tools to dissect cellular heterogeneity of complex cellular systems.